<PAGE>
                                                                 Exhibit 10.18.1


     Confidential Materials omitted and filed separately with the Securities
              and Exchange Commission. Asterisks denote omissions.

                                    AGREEMENT

This agreement is made by and between

IDENIX PHARMACEUTICALS, INC.  a corporation organized and existing under
the laws of the State of Delaware, having its principal offices located at
125 CambridgePark Drive, Cambridge, MA 02140 represented by its legal
representative Mr. Jean-Pierre Sommadossi (hereinafter referred to as
"Idenix")

                                       and

IDENIX SARL, a corporation organized and existing under the laws of France,
having registered offices in Immueuble "La Vigie" 170 rue Leon Blum, 34000
Montpellier, France, represented by its legal representative Mr. Jean-Marc
Allaire (hereinafter referred to as "Idenix SARL")

                                       and

UNIVERSITA' DELGI STUDI DI CAGLIARI, having a principal place of business at
Cittadella Universitaria, SS 554 KM 4.5, 09133 Monserrato, Cagliari, Italy,
represented by the Chancellor Prof. Pasquale Mistretta (hereinafter referred to
as the "University")

                                     whereas

a) on 4th of January 1999 the University and Idenix SARL, this last on behalf
and for the benefit of Idenix, entered into an agreement entitled "Co-operative
Antiviral Research Activity Agreement" (hereinafter referred to as "Co-operative
Agreement") aimed at performing a joined research activity in the antiviral
substances field;

b) in accordance with the Co-operative Agreement, on 14 December 2000 the
University and Idenix entered into a license agreement (hereinafter "License
Agreement") according to which the University grants to Idenix the exclusive
license for the exploitation, whether direct or indirect, of the results
obtained and that will be obtained from the performance of the activity
indicated under the previous point;

c) the above mentioned Co-operative Agreement and License Agreement have
been initially amended on 10 April 2002;

d) said agreements have been further amended with the deed undersigned by the
parties on May 8, 2003, also in consideration of the transactions at that time
pending between Idenix and Novartis Pharma AG for the acquisition, by this last,
of the majority of the shareholding of Idenix (the amendments indicated in this
point have become effective on May 8, 2003, following
<PAGE>
to the occurred execution of a "Development, License and Commercialization
Agreement" and of a "Manufacturing and Supply Agreement" by and among Idenix,
Idenix (Cayman) Limited and Novartis);

e) in compliance with the provision set forth under art. 9.1 of the
Co-operative Agreement, art. 3 of the License Agreement states that Idenix
shall pay to the University earned royalties at a rate equal to

      (i)   [**]% of Net Sales in case of direct exploitation of the results
            obtained from the performance of the research activity in accordance
            with Co-operative Agreement;

      (ii)  [**]% of Sublicense Payments or Royalties in case of
            sublicense of the Intellectual Property Rights

now, therefore, in consideration of the premises and the mutual covenants herein
contained, Idenix, Idenix SARL and the University agree as follows:

1.  The premises shall represent an integral and substantial part of this
agreement.

2.  Also in consideration of the relevance of the results that the parties
are obtaining from the joined research carried out, the royalty rate
payable by Idenix or any of its subsidiaries indicated under art. 9.1 of
the Co-operative Agreement and art. 3 of the License Agreement shall be
increased from [**]% to [**]%.

The parties hereby furthermore agree that such an increased royalty rate shall
apply to technology and other property that becomes initially subject to patent
applications (including US provisional applications) which constitute the parent
case filed on or after 14 May 2003.

For the purposes of this point 2, the date of the first filing of each parent
case patent application shall be considered (not the date of the corresponding
foreign extensions).

The parties hereby agree that the rate of royalty will be exclusively determined
by reference to the date of filing of the parent application.

3. The percentage defined under previous point 2 shall be calculated on Net
Sales whether performed directly by Idenix or by a sublicense. As regards to
patent applications, including US provisional patent applications, filed before
14 May 2003, from the execution date of the present agreement, the [**]% royalty
shall as well be calculated on Net Sales whether performed directly by Idenix or
by a sublicense. For the purpose of this section 3, the definition of "Net
Sales" provided under section 1.10 of the License Agreement shall apply.

3.1. Idenix shall provide the University of Cagliari with the right of a yearly
audit to check the correct undertakings and fulfillments of any obligations of
the Cooperative Agreement, of the License and relevant amendments.

4. The present document represents an amendment to art. 9.1 of the Co-operative
Agreement and to art. 3 of the License Agreement that, with reference to any
other provision, shall entirely apply in the current version (and with the
possible amendments that might be brought in the future) to the relationships
existing among the parties (and with the possible amendments brought in the
<PAGE>
future). The parties however agree that in any case in which it is provided to
the University the right to grant non exclusive licenses, this has to be
understood both as non exclusive and exclusive license right.

5. The parties hereby agree that the patents filed by or on behalf of Idenix or
Novartis in order to protect the results of the activity performed in pursuance
of the Cooperative Agreement, are therefore deemed subject to the terms of the
License Agreement and shall be included in the Annex to the License Agreement. A
copy of Annex A as it is currently constituted is attached hereto and made a
part of the License Agreement. The Annex A attached hereto supercedes in its
entirety the Annex A referred to in the amendment dated 10 April 2002 of the
License Agreement and Co-operative Agreement. In the future, Idenix will provide
to include in such Annex the new patent applications concerning results obtained
within the Cooperative Activity, providing the University with a quarterly
communication of such Annex including the new patent applications which updated
Annex A will be deemed to be agreed to by the University.

In the Annex A attached hereto are not included the following patents: US patent
application No. 60/626184 (Sommadossi) and US patent application No. 60/326192
(Sommadossi) that were un-correctly inserted in previous Annex A of the License
Agreement, since they are not part of the Co-operative Antiviral Research
Activity Agreement due to the fact that Professor Paolo LA Colla did not
contributed, even partially, to the achievement of the relevant inventions.

6. In order to clarify the provisions set forth in the agreement undersigned by
the parties on 8 May 2003 mentioned in the premises, the parties recognize and
accept that the rights and the obligations, stated upon the Dipartimento di
Scienze e Tecnologie Biomediche by the Co-operative Agreement and by the License
Agreement (as finally amended on 8 may 2003) shall be considered exclusively
referred to the Sezione di Microbiologia e Virologia Generale e Biotecnologie
Microbioche, directed by Prof. La Colla.

7. The parties hereto agree that the initial term of the Co-operative Agreement,
as amended, shall expire on January 22, 2007 and that the Co-operative Agreement
may be renewed for additional four year periods by mutual consent of the parties
expressed in writing at least 30 days prior to the expiration of the then
current term.

8. This agreement is drafted in English, and for the sole purpose of allowing
the University to better comprehend the relevant content, in Italian, being
understand that in case of contrasts between the English version and the Italian
version, the English one shall prevail.

    June 30, 2004
--------------------------------------
    Date


   /s/Jean Pierre Sommadossi
--------------------------------------
name and appointment


IDENIX PHARMACEUTICALS, INC.


   /s/Jean Pierre Sommadossi
--------------------------------------
name and appointment
<PAGE>
IDENIX SARL


/s/ Pasquale Mistietia
--------------------------------------
Prof. Pasquale Mistietia


/s/ Pavlo LaColla
--------------------------------------
Prof. Pavlo LaColla
<PAGE>
                                    EXHIBIT A





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<CAPTION>
                                                                            PATENT /       ISSUE /
TITLE                                                 FILING   SERIAL       PUBLICATION    PUB.
& DOCKET NAME    COUNTRY   OWNER        INVENTORS     DATE     NUMBER       NUMBER         DATE        STATUS
-------------    -------   -----        ---------     ----     ------       ------         ----        ------
<S>              <C>       <C>          <C>           <C>      <C>          <C>            <C>         <C>
[**]             [**]         [**]      [**]          [**]     [**]                                    [**]
                                        P.
                                        LaColla,
IDX1006          U.S.      USC IDXINC   JP.           5/26/01  09/863,816   2003/0060400   03/27/03    Allowed
                                        Sommadossi
[**]             [**]         [**]      [**]          [**]     [**]                                    [**]
[**]             [**]         [**]      [**]          [**]     [**]                                    [**]
                                        P.
                                        LaColla,
IDX1006 CON 3    U.S.      USC IDXINC   JP.           6/20/03  10/602,692   2004/0097462   05/20/04    Published
                                        Sommadossi
                                        P.
                                        LaColla,
IDX1006 DIV      U.S.      USC IDXINC   JP.           6/20/03  10/602,693   2004/0063622   04/01/04    Published
                                        Sommadossi
[**]             [**]         [**]      [**]          [**]     [**]         [**]           [**]        [**]
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<TABLE>
<CAPTION>
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TITLE                                                 FILING   SERIAL       PUBLICATION    PUB.
& DOCKET NAME    COUNTRY   OWNER        INVENTORS     DATE     NUMBER       NUMBER         DATE        STATUS
-------------    -------   -----        ---------     ----     ------       ------         ----        ------
<S>              <C>       <C>          <C>           <C>      <C>          <C>            <C>         <C>
[**]             [**]         [**]      [**]          [**]     [**]                                    [**]
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                                        P.
                              USC       LaColla,
IDX1007CON1      U.S.        IDXINC     JP.           6/20/03  10/602,691   2004/0097461   05/20/04    Published
                                        Sommadossi
[**]             [**]         [**]      [**]          [**]     [**]                                    [**]
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<CAPTION>
                                                                            PATENT /       ISSUE /
TITLE                                                 FILING   SERIAL       PUBLICATION    PUB.
& DOCKET NAME    COUNTRY   OWNER        INVENTORS     DATE     NUMBER       NUMBER         DATE        STATUS
-------------    -------   -----        ---------     ----     ------       ------         ----        ------
<S>              <C>       <C>          <C>           <C>      <C>          <C>            <C>         <C>
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                                        J-P
                                        Sommadossi
IDX1009CON1      US CON    USC IDXINC   P LaColla     1/24/03  10/350,772   2003/0225114   12/04/03    Published
                                        M Artico
                                        M Bryant
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& DOCKET NAME    COUNTRY   OWNER        INVENTORS     DATE     NUMBER       NUMBER         DATE        STATUS
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<S>              <C>       <C>          <C>           <C>      <C>          <C>            <C>         <C>
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IDX 1031
2'-C-Methyl-3'-
O-L-Valine
Ester                                   JP
Ribofuranosyl    U.S.         USC.      Sommadossi    6/27/03  10/607,909   2004/0077587   04/22/04    Published
Cytidine for                 IDXINC     P La
Treatment of                            Colla
Flaviviridae
Infections
(NM283)

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